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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2020

Open Access 01-08-2020 | Breast Cancer | Preclinical study

The prognostic significance of BMI1 expression in invasive breast cancer is dependent on its molecular subtypes

Authors: Maryam Althobiti, Abir A. Muftah, Mohammed A. Aleskandarany, Chitra Joseph, Michael S. Toss, Andrew Green, Emad Rakha

Published in: Breast Cancer Research and Treatment | Issue 3/2020

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Abstract

Purpose

BMI1, which is a major component of the polycomb group complex 1, is an essential epigenetic repressor of multiple regulatory genes and has been identified as a cancer stem cell (CSC) marker in several cancers. However, its role in breast cancer (BC) remains to be defined. In this study, we have evaluated the prognostic significance of BMI1 among the different molecular subtypes and assessed its association with other breast CSC markers (BCSC).

Material and method

BMI1 copy number and mRNA was assessed in large and well-characterised cohorts of early-stage BC patients [METABRIC (n = 1980) and the Bc-GenExMiner (n = 9616) databases]. BMI1 protein expression was assessed using tissue microarray and immunohistochemistry in a cohort of 870 invasive BC patients with long-term outcome data and the expression of a panel of BCSC markers was monitored.

Result

BMI1 expression, prognostic significance and its association with BCSC markers were differed between molecular classes. In the luminal oestrogen receptor-positive (ER+) BC, BMI1 showed significantly higher expression compared to ER− tumours. BMI1 showed positive correlation with favourable prognostic features and it was negatively associated with the expression of key BCSC markers (ALDH1A1, CD24, CD44, CD133, SOX10 and SOX9). High expression of BMI1 was associated with longer breast cancer-specific survival (BCSS) independent of other prognostic variables. In the basal triple negative BC subtype, BMI1 expression showed positive association with CD133 and SOX10 and it was significantly associated with shorter BCSS.

Conclusion

High BMI1 expression is associated with clinicopathological variables and outcome in BC. However, this association is dependent on the molecular subtypes. Further functional assessment to detect its underlying mechanistic roles in BC subtypes is warranted.
Appendix
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Metadata
Title
The prognostic significance of BMI1 expression in invasive breast cancer is dependent on its molecular subtypes
Authors
Maryam Althobiti
Abir A. Muftah
Mohammed A. Aleskandarany
Chitra Joseph
Michael S. Toss
Andrew Green
Emad Rakha
Publication date
01-08-2020
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-020-05719-x

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